Effects of Albaconol from the Basidiomycete Albatrellus confluens on DNA Topoisomerase II-Mediated DNA Cleavage and Relaxation

Abstract

The effect of albaconol on the growth of human tumor cell, DNA topoisomerase (topo)-mediated DNA cleavage and direct DNA breakage was investigated. Albaconol inhibited significantly the growth of the human tumor cell lines K562, A549, BGC-823 and Bcap-37, the IC₅₀ values were 7.99 ± 0.4, 3.17 ± 0.89, 4.18 ± 0.14 and 7.45 ± 2.5 μM, respectively. Albaconol stabilized and increased the topo II-mediated DNA cleavable complex and inhibited the religation activity of topo II in a dose-dependent manner, but it failed to affect the activity of topo I. Albaconol directly broke pBR322 DNA at high concentrations, but there was no effect on the macromolecule of K562 cells. These results strongly suggest that albaconol targeted specifically to DNA topo II and that this is one of the mechanisms of its antitumor action; the direct action of albaconol on DNA may partly contribute to its antitumor activity at high concentrations.

Key words

Albaconol - Albatrellaceae - Albatrellus confluens - antitumor activity - topoisomerase

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